1. Field of the Invention
The present invention relates to a hybridization system, and more particularly, to a hybridization system in which operations for hybridization of a biochip, such as sample diffusing, sample agitating, chip washing, and chip drying are automized.
2. Description of the Related Art
A biochip is formed by affixing on a support a bimolecular probe to be analyzed with high density. The biomolecular probe may be DNA, protein, or the like. By detecting whether the probe is hybridized with a target material contained in a sample, gene expression characteristics, genetic defects, protein distribution, reaction characteristics, or the like can be analyzed. Biochips are categorized into DNA chips, protein chips, and the like according to the type of probes used. In addition, biochips are categorized into micro-array chips affixed on solid supports and lab-on-a-chips affixed on micro-channels according to affixed subjects. Biochips require a hybridization chamber, an agitation system, and a washing/drying system to attain effective hybridization between the target materials contained in the sample and the probe.
Conventionally, hybridization is manually performed in a hybridization chamber formed between a slide glass and a cover glass illustrated in FIG. 1. This results in variations in experimental conditions according to users, a long testing time of 16 to 17 hours, and the requirement of up to 100 μl or less of a sample.
In order to overcome these disadvantages, an automatic system in which hybridization, washing, and drying are automatically performed has been developed. The use of the automatic system using fluctuation results in an increase of hybridization efficiency, a decrease in variations among users, a short testing time of 2 hours or less, and the requirement of only up to 50 μl or less of a sample.
FIGS. 2A and 2B are views of a conventional automatic hybridization system developed by Affymetrix Co. disclosed in U.S. Pat. No. 6,391,623. Referring to FIGS. 2A and 2B, a hybridization chamber is connected to a pump by a fluid delivery system, and hybridization is facilitated by the circulation of a fluid. In addition, sample loading, agitation, washing, and drying are performed in a single system. However, for this apparatus, a large amount of the sample is needed due to the use of a peristaltic pump and a circulation fluid channel. Because of this, after hybridization is performed for 16 hours, the DNA chip is washed and dried using a rotary oven. In addition, only the chip obtained from Affymetrix Co can be used in the cartridge, that is, this apparatus is incompatible.
FIGS. 3A and 3B are views of a conventional automatic hybridization system developed by Tecan Co. disclosed in US 20030013184. Referring to FIGS. 3A and 3B, the agitation of the solution and drying of a slide are performed on a board, and after the sample is injected, hybridization, washing, and drying are automatically performed. Two ends of a hybridization chamber are connected to two channels, and each of the channels includes a membrane for agitation and two micro pumps to facilitate hybridization between probe affixed on the chip and the target solution. For effective agitation in the chamber, the sample is mixed after filling a target solution up to a cover of the chamber so that the hybridization chamber is seriously contaminated.
FIGS. 4A and 4B are views of a conventional automatic hybridization system developed by Memorec Co. Referring to FIGS. 4A and 4B, after the sample is injected, hybridization, washing, and drying are automated. The hybridization system includes a diaphragm pump used to attain active circulation. In this case, however, a large amount of the sample, up to 220 μl, is needed because the sample must be circulated.
FIGS. 5A and 5B are view of a MAUI hybridization system obtained from Biomicro Co. Referring to FIGS. 5A and 5B, four chips can be tested in the same conditions. In this case, however, after attaching a patch or a gasket onto the chip and injecting the sample, washing and drying must be performed separately.
FIGS. 6A and 6B are views of a hybridization system obtained from Genomic Solution Co. disclosed in U.S. Pat. No. 6,432,696. Referring to FIGS. 6A and 6B, the flow and temperature of a fluid in a plurality of chips are controlled. In this case, however, the hybridization system does not include an agitation device to diffuse the sample.
As a result of research conducted to solve these problems occurring in the conventional hybridization systems, the inventors of the present invention have found that an automatic hybridization system can be implemented by controlling a pump and valves in a closed system and completed the present invention.